Important Interactions
Reviewed supplement and medication pairs classified as avoid, use with caution, or monitor -- each linking to its full sourced interaction page.
These classifications come directly from the sourced evidence behind each pair -- they are not a ranking of every possible combination. A pair that is not listed here has either not yet been reviewed, or was reviewed and no documented interaction was identified in the sources checked. Neither of those is the same as "safe" -- see methodology and the medical disclaimer. For sourced timing/spacing considerations specifically, see Timing & Absorption.
Avoid combining
Avoid combining
Sources document a clinically significant reason these should generally not be combined without a clinician's guidance.
Lisinopril + Losartan
Avoid combiningLisinopril's FDA label names losartan directly, describing a clinical trial in which combining the two increased hyperkalemia and kidney injury, and instructs to avoid combining RAS-acting drugs in general.
Spironolactone + Potassium
Avoid combiningSpironolactone's FDA label directly advises against taking potassium supplements while on this medication, due to the risk of dangerously high potassium levels.
Use caution
Use caution
Sources document a real interaction that warrants care -- dose adjustment, spacing, or professional guidance before combining.
Ashwagandha + Escitalopram
Use cautionA 2025 American Academy of Neurology conference abstract reported a single case of serotonin syndrome in a person taking escitalopram who consumed high-dose ashwagandha.
Sertraline + Aspirin
Use cautionAspirin is named directly on sertraline's FDA label as increasing bleeding risk when combined.
Aspirin + Warfarin
Use cautionAspirin is named directly on warfarin's FDA label as an antiplatelet agent that increases bleeding risk, with a specific combined-therapy regimen described for certain patients.
Ibuprofen + Aspirin
Use cautionIbuprofen can interfere with aspirin's antiplatelet protection, but the FDA-documented timing relationship depends on aspirin's formulation and dosing order -- there is no single universal spacing rule.
Aspirin + Escitalopram
Use cautionEscitalopram's FDA label names aspirin directly as adding to a documented bleeding-risk warning.
Aspirin + Vitamin E
Use cautionVitamin E's own NIH fact sheet connects aspirin use to an observed bleeding-risk finding in high-dose vitamin E users.
Atorvastatin + Warfarin
Use cautionAtorvastatin is listed as a CYP3A4 inhibitor on warfarin's FDA label, a class that can increase warfarin's effect.
Caffeine + Warfarin
Use cautionCaffeine is listed as a CYP1A2 inhibitor on warfarin's FDA label, a class that can increase warfarin's effect.
Calcium + Levothyroxine
Use cautionCalcium can reduce how much levothyroxine your body absorbs -- the FDA label recommends spacing them at least 4 hours apart.
Ciprofloxacin + Calcium
Use cautionCalcium can reduce how much ciprofloxacin your body absorbs -- FDA labeling recommends spacing them several hours apart.
Doxycycline + Calcium
Use cautionCalcium can reduce how much doxycycline your body absorbs -- FDA labeling documents this directly.
Ciprofloxacin + Zinc
Use cautionZinc can reduce how much ciprofloxacin your body absorbs -- NIH guidance recommends spacing them several hours apart.
Ciprofloxacin + Warfarin
Use cautionCiprofloxacin can enhance warfarin's blood-thinning effect -- named directly on ciprofloxacin's FDA label.
Ciprofloxacin + Iron
Use cautionIron can reduce how much ciprofloxacin your body absorbs -- FDA labeling recommends spacing them several hours apart.
Ciprofloxacin + Magnesium
Use cautionMagnesium can reduce how much ciprofloxacin your body absorbs -- FDA labeling recommends spacing them several hours apart.
Ibuprofen + Ciprofloxacin
Use cautionCiprofloxacin's FDA label warns that NSAIDs like ibuprofen, combined with very high quinolone doses, provoked convulsions in pre-clinical studies.
CoQ10 (Coenzyme Q10) + Warfarin
Use cautionCoQ10 may decrease warfarin's blood-thinning effect -- named directly on warfarin's FDA label.
Doxycycline + Iron
Use cautionIron can reduce how much doxycycline your body absorbs -- FDA labeling documents this directly.
Doxycycline + Magnesium
Use cautionMagnesium can reduce how much doxycycline your body absorbs -- FDA labeling documents this directly.
Doxycycline + Zinc
Use cautionZinc may reduce doxycycline absorption -- zinc's own NIH fact sheet discusses tetracycline-class antibiotics as a group.
Sertraline + Escitalopram
Use cautionBoth escitalopram's and sertraline's FDA labels name "other SSRIs" directly as a serotonin syndrome risk when combined with an SSRI.
Escitalopram + Warfarin
Use cautionWarfarin's FDA label names escitalopram by name as a drug that can increase bleeding risk.
Escitalopram + St. John's Wort
Use cautionEscitalopram's FDA label names St. John's Wort by name as raising serotonin syndrome risk.
Ibuprofen + Escitalopram
Use cautionEscitalopram's FDA label names NSAIDs like ibuprofen directly as adding to a documented bleeding-risk warning.
Ibuprofen + Sertraline
Use cautionSertraline's FDA label names NSAIDs like ibuprofen directly as increasing bleeding risk when combined.
Ibuprofen + Spironolactone
Use cautionSpironolactone's FDA label has a dedicated NSAID section warning that ibuprofen and other NSAIDs can raise potassium and reduce spironolactone's effectiveness.
Ibuprofen + Warfarin
Use cautionWarfarin's FDA label names ibuprofen by name as a drug that can increase bleeding risk.
Levothyroxine + Iron
Use cautionIron can reduce how much levothyroxine your body absorbs -- FDA labeling recommends spacing them at least 4 hours apart.
Lisinopril + Spironolactone
Use cautionCombining lisinopril and spironolactone can raise potassium to dangerous levels -- named directly on both drugs' FDA labels.
Spironolactone + Losartan
Use cautionSpironolactone's FDA label names angiotensin receptor blockers -- the drug class losartan belongs to -- as a specific risk factor for combined high potassium levels.
Omeprazole + Warfarin
Use cautionOmeprazole can increase warfarin's effect and bleeding risk -- named directly on omeprazole's FDA label with a monitoring recommendation.
Sertraline + St. John's Wort
Use cautionCombining sertraline with St. John's Wort raises the risk of serotonin syndrome -- named directly on sertraline's FDA label.
Sertraline + Warfarin
Use cautionSertraline is named directly on warfarin's FDA label as a drug that can increase bleeding risk.
Warfarin + St. John's Wort
Use cautionSt. John's Wort can weaken warfarin's blood-thinning effect -- this is named directly on warfarin's FDA label.
Vitamin K + Warfarin
Use cautionVitamin K intake needs to stay consistent while taking warfarin -- it does not need to be avoided.
Monitor
Monitor
Sources document an interaction worth watching for -- monitoring a lab value, symptom, or effect while combining.
Amlodipine + Metformin
MonitorMetformin's FDA label names calcium channel blockers -- the drug class amlodipine belongs to -- among medications that can raise blood sugar.
Amlodipine + Ashwagandha
MonitorAshwagandha is named by NCCIH as a supplement that may interact with high blood pressure medications, of which amlodipine is one.
Lisinopril + Ashwagandha
MonitorAshwagandha is named by NCCIH as a supplement that may interact with high blood pressure medications, of which lisinopril is one.
Spironolactone + Ashwagandha
MonitorAshwagandha is named by NCCIH as a supplement that may interact with high blood pressure medications; spironolactone is FDA-labeled as an add-on hypertension treatment.
Levothyroxine + Ashwagandha
MonitorAshwagandha is named directly by NCCIH as a supplement that may interact with thyroid hormone medications like levothyroxine, and is specifically cautioned against for people with thyroid disorders.
Metformin + Ashwagandha
MonitorAshwagandha is named by NCCIH as a supplement that may interact with diabetes medications, of which metformin is one.
Ashwagandha + Losartan
MonitorAshwagandha is named by NCCIH as a supplement that may interact with high blood pressure medications, of which losartan is one.
Lisinopril + Aspirin
MonitorAspirin's own FDA label names RAS inhibitors, the drug class that includes lisinopril, as a documented interaction affecting kidney function and blood pressure control.
Aspirin + Levothyroxine
MonitorLevothyroxine's FDA label describes an effect of high-dose salicylates on thyroid hormone lab measurements, at doses well above typical aspirin use.
Spironolactone + Aspirin
MonitorSpironolactone's FDA label has a dedicated section stating that aspirin can reduce spironolactone's effectiveness.
Melatonin + Aspirin
MonitorNCCIH names blood thinner medications, a class aspirin belongs to, as needing medical supervision when combined with melatonin.
Aspirin + Losartan
MonitorLosartan's MedlinePlus guidance names aspirin directly as a nonprescription product that may interact.
Atorvastatin + CoQ10 (Coenzyme Q10)
MonitorAtorvastatin has been shown to lower blood CoQ10 levels in a clinical study.
Atorvastatin + St. John's Wort
MonitorNCCIH names "certain statins, including simvastatin" among the medications St. John's Wort can weaken -- atorvastatin is a statin, though it is not named individually.
Atorvastatin + Vitamin C
MonitorVitamin C's own fact sheet names statins -- the drug class that includes atorvastatin -- as medications it may interact with.
Calcium + Caffeine
MonitorCaffeine may interfere with how much calcium your body absorbs.
Ciprofloxacin + Caffeine
MonitorCiprofloxacin reduces how quickly your body clears caffeine -- named directly on ciprofloxacin's FDA label.
Calcium + Iron
MonitorCalcium may reduce how much iron your body absorbs from a supplement or meal.
Calcium + Omeprazole
MonitorLong-term, high-dose omeprazole use is associated with an increased risk of bone fracture -- its FDA label documents this directly.
Copper + Zinc
MonitorTaking high doses of zinc supplements for a long period can reduce copper absorption and lead to copper deficiency.
Vitamin B12 + Folate / Folic Acid
MonitorFolate's own NIH fact sheet warns that high-dose folate supplements can hide the signs of a vitamin B12 deficiency.
Ibuprofen + Lisinopril
MonitorLisinopril's FDA label names ACE inhibitors like lisinopril directly in its NSAID drug-interaction section, warning of reduced kidney function and blunted blood-pressure control.
Ibuprofen + Losartan
MonitorLosartan's FDA label names losartan directly in its NSAID drug-interaction section, warning of reduced kidney function and blunted blood-pressure control.
Omeprazole + Iron
MonitorOmeprazole can reduce iron absorption -- named directly on its FDA label as a drug dependent on gastric pH.
Zinc + Iron
MonitorHigh doses of iron can reduce how much zinc your body absorbs.
Sertraline + Levothyroxine
MonitorStarting sertraline can increase how much levothyroxine you need -- named directly on levothyroxine's FDA label.
Omeprazole + Levothyroxine
MonitorOmeprazole, as a proton pump inhibitor, may reduce levothyroxine absorption -- named on levothyroxine's own FDA label at the drug-class level.
Magnesium + Levothyroxine
MonitorMagnesium-hydroxide antacid products (not standalone magnesium supplements) can reduce levothyroxine absorption.
Lisinopril + Potassium
MonitorLisinopril can raise potassium levels -- its FDA label recommends monitoring, particularly if combined with a potassium supplement.
Losartan + Potassium
MonitorLosartan's FDA label directly advises against using potassium supplements without a doctor's guidance, due to the risk of high potassium levels.
Magnesium + Zinc
MonitorVery high doses of supplemental zinc can reduce the body's absorption of magnesium.
Magnesium + Omeprazole
MonitorOmeprazole use can lower magnesium levels -- its FDA label documents this directly and recommends monitoring in some patients.
Melatonin + Warfarin
MonitorNCCIH names blood thinner medications, a class warfarin belongs to, as needing medical supervision when combined with melatonin.
Vitamin B12 + Metformin
MonitorLong-term metformin use can lower vitamin B12 levels -- its FDA label recommends periodic monitoring, not avoidance.
Omega-3 / Fish Oil + Warfarin
MonitorNIH's own fact sheets name warfarin as the one documented drug interaction for omega-3 supplements, due to a possible added bleeding/anticoagulant effect.
Vitamin B12 + Omeprazole
MonitorLong-term omeprazole use can reduce vitamin B12 absorption -- its FDA label documents this directly.
Omeprazole + Potassium
MonitorOmeprazole's label advises telling your doctor if you have low potassium levels before starting treatment.
Vitamin C + Vitamin E
MonitorA clinical trial that combined vitamin E and vitamin C in women with existing heart disease found no cardiovascular benefit and higher all-cause mortality than placebo, though vitamin C also plays a normal role in regenerating vitamin E in the body.
Vitamin K + Vitamin E
MonitorMedlinePlus states directly that vitamin E can interfere with how vitamin K works in the body.
Warfarin + Vitamin E
MonitorVitamin E's own NIH fact sheets specifically name warfarin as a bleeding-risk interaction at higher supplemental doses.
Not sure where your combination falls? Check it directly, or browse Supplement Safety and Medication Safety for broader guidance.